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Science and Social Context: The regulation of recombinant bovine growth hormone (rbGH) in the United States and Canada, 1982-1998

Lisa Nicole Mills

A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Graduate Department of Political Science University of Toronto

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The author retains ownership of the L'auteur conserve la propriete du copyright in this thesis. Neither the droit d'auteur qui protege cette these. thesis nor substantial extracts fkom it Ni la these ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent Etre imprimes reproduced without the author7s ou autrement reproduits sans son permission. autorisation. Abstract Science and social context: The regulation of recombinant bovine growth hormone (rbGH) in the United States and Canada, 1982-199s Doctor of PhiIosophy 1999 Lisa Nicole Milk Graduate Department of Political Science University of Toronto

This dissertation explores the relationship between science arid public policy in the case of recombinant bovine growth hormone (rbGH), a geneticallyengineered drug which increases milk yield in cows. The product was approved by the United States Food and Drug Administration in 1993; it has not been approved in Canada. In both countries, the debate over the product's safety has been intensely controversial. The dissertation argues that problems in the relationship between science and policy arise at the point when judgements are made about the scientific evidence. Although there was agreement about the scientific evidence across institutions, the interpretation of that evidence diverged depending on the context from which it was viewed, The dissertation uses Helen Longino's concept of contextual empiricism to explain the varying outcomes in different settings. Scientists' conception of the kind of evidence required to make a judgement about product safety, and their interpretation of that evidence, was guided by the background assumptions they brought to it. These assumptions were context-dependent, however, with the resuIt that policy responses differed between the U.S. and Canada, and the assumptions themselves were the subject of conflict in both countries. The difference in the U.SJCanadian response is the most obvious example of a contrast in the assessment of the drug's introduction. The dissertation also examines differing interpretations between the academic, corporate, and regulatory settings in order to elucidate the science and policy relationship. The dissertation contributes to the literature on science and public policy by examining the process by which scientists make sense of empirical evidence. It argues for the relevance of the concept of contextual empiricism for understanding the science-policy relationship. It has attempted a theoretical synthesis, drawing on concepts from the history and philosophy of science and political economy to better understand this relationship. The concept of contextual empiricism accounts for both the degree of consensus about the evidence, and the degree of divergence in its interpretation, between institutions and jurisdictions. Acknowledgements

I would like to thank my supervisor, Professor David Wok, for his support and encouragement, and the members of my committee, especially Professor Liora Salter. I also wish to acknowledge all of the individuals whom I interviewed as part of the thesis research, particularly officials at the U.S. Food and Drug Administration, who were generous with their time both during the interviews and in subsequent cof~llllunications. The following institutions and individuals also made important contributions to the completion of the thesis: the Toronto Food PoLicy Council gave me access to its library; Dr. Alison Weir tutored me in statistics; Dr. Magi Abdul-Masih assisted me with understanding concepts in biochemistry; and Patricia Fleck gave valuable assistance with the typing of the bibliography and checking of interview quotes. The thesis was written with financial support from the University of Toronto Open Fellowship, and a School of Graduate Studies Travel Grant- Many thanks to my family and friends for their support, particularly the Loretto Sisters, Extended Community, Leadership Team and staff, whose kindness and generosity have sustained me over the last five years; and to Leslie Crawford; Catherine and Peggy Lathwell; Katie Isbester; Mary-Beth Raddon; Joe Murray, and especially Deborah C lipperton. Table of Contents

.0 Abstract...... 11 Acknowledgements ...... iv Acronyms ...... VIII

Chapter One: Introduction I . Introduction...... 1 2 . Literature review ...... 8 2 1. Science and pubIic policy literature...... 8 2.2. Philosophy of Science Literature ...... 14 2.3. Political economy of agriculture literature ...... 18 3 . Methodology ...... 23 4- Chapter Outline ...... 26

Chapter Two: The economic context: The political economy of agricultural biotechnology

Introduction ...... 28 Regulatory Changes and the Commercialization of Genetic Research ...... 29 Commercialization and biotechnology ...... 31 'A 95-year old stamp company": Monsanto and biotechnology...... -36 Monsanto and rbGH ...... ,...... 44 University Scientists and rbGH research ...... 53 Conclusion ...... , ...... *...... -58

Chapter Three: The U.S. context Introduction ...... 60 The U.S. experience . overview ...... 60 The U.S. Regulatory System ...... 68 Biotechnology: The Regulatory Environment in the 1980s...... 68 Animal Drug Laws and the rbGH review ...... 71 Milk labelling ...... 87 Approval ...... -91 Conclusion ...... ,,...... -98

Chapter Six Conclusion

1. The interpretation the evidence.,.*.*.*...... *...... --....-. ....*...... -209 2. Conclusion...... --..------.--.---AA 730 References..,...... -.-...,...... 233 Interviews...... 263

vii Acronyms CAC - Codex Alimentarius Commission CDC - Canadian Dairy Commission BVD - Bureau of Veterinary Drugs (Canada) CEPA - Canadian Environmental Protection Act CMSMC - Canadian Milk Supply Management Cornrnittee CVM - Center for Veterinary Medicine (US.) FA0 - United Nations Food and Agriculture Organization FDA - Food and Drug Administration FFDCA - Federal Food, Drug, and Cosmetic Act (US.) FOI - Freedom of Wormation

GAO - General Accounting Office

INAD - Investigational New Animal Drug Application JECFA - Joint WHO/FAO Expert Committee on Food Additives NADA - New Animal Drug Appbcation NADE - Office of New Animal Drug Evaluations (US) NBAC - National Biotechnology Advisory Committee (Canada)

NOC - Notice of Compliance (Canada) OSTP - Office of Science and Technology Policy PAMP - Post-Approval Monitoring Program TFPC - Toronto Food Policy Council VMAC - Veterinary Medicine Advisory Committee (U.S.) WHO - World Health Organization Chapter One

Introduction 1. Introduction

On January 14 1999, Health Canada rejected Monsanto's application to license recombinant bovine growth hormone (rbGH) in Canada. (The drug is also known as recombinant bovine somatotropin (rbST) or simply bovine sornatotropin @ST)).l The product is developed using recombinant DNA (rDNA) technology, a form of biotechnology. When injected into lactating dairy cows, the product results in a 10-1 5% increase in miUc production.' In the early 1980s, four multinational chemical and pharmaceutical companies competed to bring the product to market - Monsanto, a chemical corporatiod based in St. Louis, Missouri; Elanco, the animal products division of ELi Lay, a pharmaceutical corporation; Upjohn, also a pharmaceuticals producer; and American Cyanamid, a pesticides producer. By 1998, however, only Monsanto's application was active in Canada. Health Canada's decision was made on the grounds that although the drug posed

Little risk to human health, animal health was jeopardized. It was announced after nine years

' Even the name has been controversial. Early scientific reports refer to the naturallyderived hormone as bGH (see Bauman et al. 1982; Eppard et al. 1985). In later years, the product manufacturers, proponents, and regulators have referred to the natural version as "somatotropin," or bST (the dictionary definition of somatotropin is "growth hormone") and to the recombinant product as recombinant bovine somatotropin or rbST (although this is usually shortened to bST). Opponents, on the other hand, refer to it as recombinant bovine growth hormone, or rbGH- The drug's proponents believe that the term "growth honnone" associates the drug with steroid hormones and thus misrepresents the nature of the product, which is a protein, (Steroid hormones act directly on the cell, whereas protein hormones cause cellular responses by binding to the cell surface. Steroids survive digestion whereas proteins do not). Although some company representatives contend that only "somatotropin" is the correct scientific term, the pituitary hormone was called "growth hormone" and scientific reports refer to the recombinant product as growth hormone, including the FDA's summary of the human health data. (See Juskevich and Guyer 1990: also Burton et al. 1994) The use of the term "somatotropin" in preference to "growth hormone" seems to date from around 1986 - at the U.S. House of Representatives hearings in 1986, it was stated that the term "somatotropin" had been coined by industry to get away from the negative associations with the word hormone (U.S.House of Representatives 1987: 2). I use the terms rbGH and rbST interchangeably, but generally I: use the term rbGH. I also use the terms "somea-ibove" and Posilac to refer to Monsanto's product formulation, the only product of its type approved for use in the US. ' Initial estimates were much higher - later reports indicate that this range is more likely. Monsanto spun off its chemical division in 1997, hence the term "chemical corporation" no longer accurately describes the company. This will be discussed in Chapter Two. of review. The last six months of that review have been particularly turbulent, as Senate hearings probed the decision-making process, and scientists alleged that they had been pressured by the company, and senior management, to approve the drug in spite of their own misgivings. This case study, therefore, is a useful one for understanding the complexities of the science-policy relationship. Health Canada's rejection of the drug stands in contrast to the U.S. Food and Drug Administration (FDA) approval in 1993. The difference between the U.S. and Canadian regulatory response is one of the puzzles which the thesis explores. However, this puzzle is intended to ilIustrate the natme of the reIationship between science and policy. A different approach could have been taken. It would have been possible to focus on the difference between the two countries &om an institutional perspective in order to analyze the impact of institutions on a particular policy outcome. However, my approach has been to examine the impact of institutions on the way that scientif~cevidence is produced and interpreted. It is the production and interpretation of evidence in the policy context that is the focus of the thesis. I argue that although there was agreement among the various actors regarding what the evidence showed, the interpretation of that evidence diverged, depending on the context from which it was viewed. In making this argument, I rely on Helen Longino's (1990) concept of contextual empiricism. Longino suggests that judgements about empirical evidence are based on background assumptions we bring to its assessment; these assumptions are related to the context in which those judgements are formed. Therefore, I argue that in order to understand the relationship between science and policy, we must look at the expectations and assumptions which guide the interpretations made by scientists. Given this focus on scientists' perceptions, it is possible to argue that the outcome could be explained in tern of the individual personalities involved. However, I argue that these perceptions are shaped by context in two different senses. First, the goals and mandate of the institution in which the scientist operates exert a particular kind of pressure on him or her, thereby promoting or constraining particular types of choices. Second, the broader

poLitical-econonic cofiicjct also affects scientists' interpretations. The two factors which were most sibmcant here were the nature of the dairy system, and the significance of the biotechnology industry. In order to assess the likely effect of a product, scientists must have some knowledge of the social context into which the drug is to be introduced, and an implicit acceptance of the values inherent in that context, Scientists in all contexts - regulatory, corporate, and academic - start fkom a base of existing scientific knowledge, what Kuhn (1970) terms "normal" science. The extent to which scientists question the assumptions from normal science is affected by the context in which they operate, however. Regulatory scientists' mandate precludes basic research. Their communication with those outside the regulatory body is restricted by the need to maintain the confidentiality of proprietary information. They are conscious of the time limitations that they work within, md the importance of timeliness to their career prospects. They are also conscious of corporate costs and competitive pressures. Regulatory scientists

are expected to fuLfi their mandate to protect public health, on the one hand, and to avoid imposing an undue regulatory burden on corporations, on the other. They are therefore caught in a juncture between the requirements of the regulatory body, and broader corporate and pubLic pressures. Under these circumstances, regulatory scientists decide what kind of evidence can "reasonably" be requested fiom the company. Reviewers' definition of safety was bounded by distinctions between what was reasonable and unreasonable, which in turn reflected distinctions made in conventional science. If the degree of risk can already be explained on the basis of existing knowledge, they are unlikely to ask for further data. In both Canada and the U.S., it was decided that long-term human health testing was unnecessary because the likelihood of risk was already known to be Iow. An additional two-week feeding study was conducted as a result of politicd pressure rather than scientific doubt. This decision was questioned by critics and, in Canada, by scientists within the Health Protection Branch. The approach taken by readatory scientists can be contrasted with that of scientists engaged in basic research, who are more likely to question the assumptions from conventional science and to require empirical support for then Basic scientists are also more likely to acknowledge the limitations of their experimental method, rather than to make comparisons with the existing context in order to generalize from limited experimental data Corporate scientists, on the other hand, are also likely to rely on conventional knowledge and to rely on contextual knowledge to downplay risk and arnbi-pity even fiuther. In the rbGH case, corporate scientists claimed that not only was there no risk fiom increased levels of growth factor in miLk, but there was no increase in growth factor, In the thesis, I examine the methodology and conclusions of corporate and academic science in order to contrast this with the reagdatory review process, and in order to explore the development of positions which fed into the policy debate. The relevance of the broader political-economic context can be seen in the decision on animal health. With regard to animal health, the difference between the US. and Canada becomes salient. Reviewers in both countries decided that the animal health data showed problems that were both statistically and biologically significant. The scientists differed in their assessment of the extent of the problem, however. Ln the US., animal health effects were also determined to be manageable, a judgement which depended on knowledge about existing dairy practices, and the implicit acceptance of their viability. AU technologies require that we adapt our behaviour in some way. The adaptation of behaviour required by the introduction of rbGH reinforced a system of dairy production which is reliant on technologies such as antibiotics and reproductive drugs. Existing dairy practices were factored in to the studies themselves, in which reviewers required a balance between a "scientific" study and a "realistic" study which would reflect actual conditions on the farm. Actual conditions on the farm were taken to include the use of what are known as "extra- label" drugs, that is, drugs which have been used in ways which violate their conditions of approval. The data fiom these studies still showed that problems increased, but it was concluded that a "successful" farmer, who was managing existing problems, could also manage these. A successful farmer, as a series of Office of Technology Assessment (OTA) reports pointed out, was located in the south or south-west of the country, producing on an industrial dairy of between 500 and I500 cows. When you have more animals in larger units, the possibility of disease is higher, and so is the resultant use of antibiotics. Since the rbGH decision, the US. has also introduced legislation which has legitimized the use of extra-label drugs. The FDA's assessment placed the ultimate responsibility for managing animal health problems with the farmer, and the institutions for monitoring drug residues in the milk supply. In Canada, on the other hand, animal health problems were regarded as "severe" rather than subtle, and it was the regdators, rather than the farmers, who were seen as responsible for protecting animaI welfare and the viability of Canadian farms. The consequences of increased disease rates were viewed in terms of the supply management system; if antibiotic use resulted in milk disposal, the farmer would be unable to produce in accordance with quota requirements. The political economy of agriculture literature is useful here in understanding agricultural production. Although valid criticisms of the Literature have been made, there are important insights from the literature which are relevant here. One is that agricultural production needs to be considered in its relation to other forms of capitalist production. The other is that the form of domestic agriculture is related to the nature of the prevailing international re,Matory regime. Domestically-based systems of agricultural production and protection are not merely the consequence of policy-making at the national level, but of international systems of reaplation which permit or inhibit certain types of domestic policy. The post-world war two economic order encouraged the development of policies of national regulation, based on the US. model. However, this model paradoxically facilitated the rise of agribusiness corporations whose reach extended beyond national boundaries. The rbGH case can be seen as an example of a trend toward both the industrialization and globalization of agricultural production, and varying national responses to it. The approval of rbGH in the U.S. implicitly recognized the acceptability of the industrial model and its further expansion. This model has not been universally accepted, however, and in Canada the shift of responsibility for the drug's consequences implied by this model was not regarded as acceptable. The thesis research was motivated by an empirical puzzle. I was curious about the ferocity of the safety debate regarding bovine growth hormone. How had the debate about this issue been resolved, or why had it failed to be resolved? How did scientists in different contexts reason about this issue? Although the thesis is empirically focused, it makes a theoretical contribution to the literature on science and public policy in several ways. One, it argues for the relevance of the concept of contextual empiricism for understanding the science-policy relationship. Two, the thesis has attempted a theoretical synthesis, drawing on concepts fiom the history and philosophy of science and political economy to better understand this relationship. This adds to the insights from the science-policy literature and suggests that empirical fmdings fiom the case study may be used to re-think the fmdings from this literature. For example, Liora Salter's (1988) and Sheila Jasanoff s (1986) work, distinguish "normal" science from science used for public policy purposes. The thesis concurs with the distinction between regulatory and "normal" science, but argues that paradoxically one of the factors which distinggshes it is precisely its dependence on normal science. Jasanoff s comparative-institutional perspective is also useful. Jasanoff emphasises the distribution of power among the three branches of government as a critical factor in determining the difference in scientific debate between different jurisdictions. The thesis suggests that the institutional structure in which decision-making takes pIace may influence the outcome, but in ways which are different than those suggested by this model. The U.S. model, Jasanoff notes, is more amenable to public participation and intervention, but this does not influence the decision-making process prior to public review. The recent Canadian experience raises the question of whether Congressional and public pressure may in fact have served to discourage dissent within the FDA and foreclose the kind of diversity of response which was present in Canada. The internal dissension at Health Canada highlights the deficiencies in the risk comUILication approach. (See for example Powell and Leiss, 1997) This approach locates the dif£iculty in the science-policy relationship in the communication of technical knowledge to a public which does not share the same expertise. The thesis suggests that there is not only a distinction in the perception between experts and the public, but between experts on this issue. One could perhaps explain internal dissension in terms of a lack of communication within the Department, but I believe it is an issue of differences in scientific judgement. The question of how these differences are resolved is not merely a question of communication. The thesis also argues that the communication of risk during the review process is inherently problematic under the current system. The rbGH case shows that the compIexity of scientific information is likely to be distorted in the political debate. It is also problematic when not all of the data can be discussed. The confidentiality of information creates problems both in relationship between regulators and the rest of the scientific community, and regulators and the public. Basic scientists' questions about the FDA's conclusions couId not be answered with the limited information which was released. The public's concerns were agbwvated when the release of information conflicted with the story presented by other actors in the debate, particulady university scientists and health professionals. University extension workers had promoted the product as "safe" prior to the completion of its review; when leaks of data, and subsequent official releases of information, appeared to contradict this finding, confidence in both the regulator and other public bodies was eroded. Communicating the scientif~cdebate in a way which was understandable, and yet which did justice to the complexities of the debate, was one of the challenges of the thesis. Researching the thesis was also challenging because the controversial nature of the subject, and the confidential nature of the data made it particuiarly difficult to obtain intewiews, and to obtain complete information once interviews were given. Inte~eweesoften could not refer to specific details of the case, but spoke in generalities. The content and detail of discussions within and between organizations could not be divulged. The focus on rbGH alone, as in a focus on any single case study, places certain limitations on the generalizability of the conclusions that can be drawn here. However, the very uniqueness of the case, and the confidentiality of specific details, offers greater scope for generalization because interviewees spoke generally rather than specifically. The other methodological limitation was that interviewees had the opportunity to scrutinize and veto questions before the interview took place, and to amend and delete from quotes and paraphrases fkom the interview. Most of the questions however were accepted.

Most ofthe quotes were also accepted, but not all. Sheila Jasanoff has said that "regulation..is a kind of social contract that specifies the terms under which state and society agree to accept the costs, risks and benefits of a given technological enterprise." (1995a: 3 11) The thesis explores the problematic nature of this contract and the for regulators of assessing the risks associated with a technology when there is no consensus about its benefits. 2. Literature review As discussed above, the thesis draws on insights from the science and public policy, history and philosophy of science, and political economy of agriculture literature. The following section provides a brief overview of issues in these literatures and the concepts from them which are relevant for this study.

2.1. Science and public policy literature

Some analysts have located the problems in the sciencdpolicy relationship externally to that relationship; the literature on risk communication locates the problem in the perception and transmission of information about risk For example, in Mad Cows and Mother's Milk, Douglas Powell and William Leiss (1997) have argued that science itself is relatively unproblematic; it is the communication of risk, or more precisely, its mismanagement, which results in controversy. They defme risk as "the probability of harm in any given situation," which is determined by "a) the nature of the hazard and b) the extent of anyone's exposure to the hazard." Risk communication "is the process of exchanges about how best to assess and manage risks among academics, regulatory practitioners, interest groups, and the general public" (33). When those responsible for risk assessment fail to communicate their fmdings to the public in a timely and effective manner, a risk information vacuum develops, in which fears are amplified and distorted by misinformation - " inadvertently misleading data" - and disinfomation - "deliberately rnideading data" (3 1). Risk communication is difficult because members of the public, and the experts responsible for communicating risk to them, use two different languages to represent their understanding of risk. "Public assessment" is based on people's understanding of their everyday experiences, and does not necessarily incorporate expert findings. "Expert assessment," on the other hand, is probabilistic and based on technical knowledge. The divide between "pubiic'~and "expert" assessments and linguistic forms cannot be eliminated, but can be reduced by good communication practices. Leiss and Powell explain the rbST controversy as the outcome of poor risk communication. They conclude that, in Canada, risk assessment assumptions were not made explicit; public concerns were not understood; and no agency took responsibility for transmitticg accurate information and creating a consensus. In Canada, the information vacuum resulted in "damage done to the science-based risk-assessment process by the silence of some parties and the mischief of others, who so thoroughly intermixed peripheral issues with the health risk ones so that no reasonable risk discussion was possible" (213). In the U.S., on the other hand, third parties were engaged in the risk assessment process, and re,dators communicated frequently with the public, with the result that controversy died away after the drug was approved in 1994. This interpretation cannot be sustained in the rbGH case. It is not only communication of the conclusions which has differed between the U.S. and Canada, but the conclusions themselves. Nor can the expedpublic distinction be sustained in this case; the conclusions from the evidence have been controversial even within Canada's Health Protection Branch. The case cannot be categorized as a case of poor risk communication, because there was no consensus to communicate from Health Canada. Finally, risk communication by governments and corporations is problematic when the review is ongoing. Laws which protect the confidentiality of proprietaxy information prevent the release of data which are critical to the final decision. In the rbGH case, a simple statement on anirnal health, and its human health implications, could not be arrived at before all the data were submitted and analyzed. Statements were issued by the FDA regarding human health, which may have eased controversy in the US.;however, these statements may also have inflamed it by seeming to have compromised the Agency's objectivity when the animal health review was incomplete. Other analysts, on the other hand, have not assumed that science in a public policy context is transparent, but suggest rather that scientific findings must be translated into public policy. For example, Liora Salter problematizes the concept of science in a public role and suggests that the nature of the scientific enterprise is altered by public policy involvement. Salter differentiates "mandated science" - science used for the purposes of making public policy - from conventional science (1988: 2). She states that a mandate to develop recommendations or decisions for public policy exerts a pressure on science that is reflected both in the activities of scientists and in their work or its interpretation (3). According to Salter, mandated science is a type of activity with four characteristics. It is an idealized science - that is, it is required to serve purposes that only an ideal science could Mi.It is supposed to be publicly intelligible, and to establish clear public choices for decision makers; yet it is also required to produce results which are credible to the scientific community, to be value-free, and to be an open and public exercise. It is imbued with legal considerations - decisions made on the basis of scientific evidence have sigmficant legal implications of which researchers are aware. The debates within mandated science are unique - mandated science tends to evduate scientific investigations rather than to conduct them. Scientists in a public policy role often have to address scientists as well as regulators, and different conclusions may be drawn from their fmdings by different audiences. Finally, mandated science "makes explicit the moral dilemmas posed by science". Scientists' knowledge of social, moral and legal constraints affects their recommendations (5-8). The very nature of mandated science, however, contradicts these idealized requirements. Since it has a public policy role, mandated science has a close relationship to values; because scientifk evidence is conflicting and uncertain, its conclusions often cannot be neatly divided to represent two sides of a public policy debate; and because it is mostly not published nor peer-reviewed it is not as "public" as conventional science (5). Salter argues that science and policy issues are so closely intertwined in mandated science that they cannot be di~tin~pished.Not all mandated science is controversial; however, once an issue in mandated science becomes controversial, Salter argues, it is difficult for a dispassionate assessment of it to be conducted. Once a risk issue becomes politicized, the environment in which it is assessed is fundamentally changed. Salter's work is extremely useful for understanding the pressures under which policy-relevant science is conducted. It does not, however, explain the rbGH case, and the difference in outcome in the two jurisdictions. Mandated science, Salter argues, exists in every jurisdiction; we must therefore look to factors other than those she has identiF~edin order to understand the sciencelpolicy relationship in the rbGH case. Also, in this case, scientific issues could be distinguished fiom judgements about the context into which the drug was to be introduced. The distinctions can be seen through the difference in the position of corporate, academic, and regulatory scientists working on rbGH. The rbGH controversy exerted pressures on scientists in the policy debate, but did not transform the interpretation of the data. It was the assumptions underpinning the various interpretations which led to the controversy, and which motivated the rbGH debate. Other analysts attribute the difficulties in the science and policy dationship to the nature of the policy process. From an examination of regulatory science in comparative perspective, analysts such as Sheila Jasanoff have argued that the nature and outcome of scientific debates are affected by the structure of the political system in which they take place: "a hdamental feature of political organization - the allocation of political authority among the three branches of government - heavily influences the form and intensity of scientific debates relating to risk" (1986: 5). In the United States, the f?agmentation of political power means that the regulatory process is closely supervised by both Congress and the courts. Congressional committees may convene public hearings into regulatory matters, and Congressional representatives may request that the investigative arm, the General Accounting Oftice (GAO), inquire into the conduct of the regulatory process. For exarnple:

In 1978, the FDA took part in fifty-one hearings before twenty-four different Congressional committees and subcommittees, the GAO issued eight investigative reports on issues affected by the FDA, and the Agency responded to 4,463 written inquiries from Congress. (Bricbann, Jasanoff and ngen 1985: 45) Corgwss also has sufficient resources to acquire external expertise on policy-relevant science, Regulatory action also takes place under judicial oversight? The Administrative Procedure Act of 1946 authorized the courts to overturn decisions not based on "substantial

Jasanoff has noted that the capacity of the courts to affect policy has been circumscribed in the case of biotechnology by the 1986 Coordinated Framework for the Regulation of Biotechnology (see Jasanoff 199%: 157). In the 1980s, the courts also followed a new doctrine with regard to their assessment of agencies' regulatory decisions - "the mere existence of scientific uncertainty did not justify the regulation of trivial risks." In Monsanto v. Kennedy, 1979, the DC circuit judged that although the governing statute granted agencies authority to regulate even trivial risks, the agency should not conform to this standard if the risk was insignificant (82). evidence" (Jasanoff 1995: 69). As a result of "the extraordinary judicialization of the American administrative process,;' Jasanoff states that

Agency rule-making has acquired many of the characteristics of a formal trial. As a result, individual citizens and citizen groups have unparalleled right to intervene in administrative proceedings, to question the expert judgements of government agencies, and ultimately to force changes in policy through litigation. (1986: 56)

In Parliamentary systems, in contrast, the judiciary is more reluctant to invalidate regulatory actions. There are also fewer mechanisms for opening up the regulatory process to public participation. The Freedom of Information Act in Canada, for example, is more restrictive than that in the United States, and there is no Canadian or European equivalent of the GAO. Although commissions of inquiry may investigate government action, these are rarely established, and in Parliamentary systems, the legislature is much less likely to challenge reaplatory action than in the United States. Jasanoff therefore characterizes the U.S. as "formal, open, adversarial, and confrontational," in contrast to the Canadian and European approach which is "informal, confidential, consultative, and cooperative" (56). She does not think that this degree of openness in the U.S. necessarily assists in the resolution of policy conflict, but rather prolongs the examination of evidence which cannot in itself solve a political dilemma. Habitual questioning by Congress also serves to undermine, rather than to bolster, public confidence in regulatory agencies (Briclanann, Jasanoff and Ilgen 1985: 96). Although this work sheds light on the policy process, it does not adequately explain the science and policy in the rbGH case. In this case, the nature of the political system in the US. enabled critics to use the investigative branch of Congress, as well as the investigative offices within the executive branch, to review and critique the decision-making process. Advisory committee meetings were also open for public comment. However, it is important to distinguish mechanisms for review from the decision-making process itself. JasanofT suggests a pluratistic model of decision-making, in which a number of different actors may influence the policy process. In the rbGH case, however, public hearings served to communicate and legitimize the FDA's fmdings to the public, but they did not infiuence the outcome. In order to understand the decision in this case, one needs to examine the assessment of the evidence pnbr to its public discussion. Scientists needed to come to some conclusions about the product before submitting those conclusions for review; it is this process which the thesis examines. The institutional differences in the policy process explain neither the outcome, nor the duration, of the controversy in the two countries; this would lead one to expect that a decision would have been reached in Canada before the U.S. 2.2. Philosophy of Science Literature Since my primary concern is with the science/policy relationship, I do not explore the issues raised in the philosophy of science iiterature extensively; however, I draw on the work of two thinkers whose concepts are germane to the rbGH case. In The Structure of Scientzjk Revolutions, Kuhn (1 970) argued that although empirical evidence restricted the number of possible scientific accounts of a particular phenomenon, it could not fully explain the prevalence of any particular account. In order for observations to make any sense to the observer, they have to be assimilated into a paradiap - an overarching structure of established evidence and belief which defmes natural entities and their interaction, and guides future research about them. ‘‘Normal" science is circumscribed by the boundaries of the paradigm; it is ""firmly based upon one or more past scientific achievements, achievements that some particular scientific community acknowledges for a time as supplying the foundation for its further practice." (1970: 10) Observation, therefore, is theory-laden: scientists defme the natural world in terms drawn from pre-existing theory. The use of terminology in one theory may therefore have a different meaning, and refer to different entities, than the same terminology in another theory. Consequently, theories are incommensurable with one another, because the phenomena they refer to are different. The process of paradigm creation is social as well as "'scientific." No paradigm can account for every instance of a phenomenon; counter-instances can always be found, and can always be taken as evidence for an alternative viewpoint. In order to get on with the work of doing normal science, its practitioners cannot puzzle over every counter-instance. It is when these counter-instances conflict with scientists' fundamental theoretical commitments, or their attempts to solve a practical problem, that a new paradigm is likely to arise. New paradigms are created when anomalies become appareot; that is, when there are an increasing number of observations for which existing theories can no longer account. Anomalous observation coincides with conceptual construction; an unexpected occurrence cannot be recognized as posing a threat to the existing paradigm without the simultaneous development of concepts to account for it. The awareness of anomaly is necessary, but not sufficient, for the establishment of an alternative framework. In order for the new paradigm to displace its predecessor, it must be accepted by the community of scientists, a process which depends as much on persuasive power as rational assessment New explanations are initially resisted by adherents to conventional knowledge. They do not become paradigmatic until they are accepted by the majority of practitioners, a practice of persuasion and conversion which cannot be fully accounted for, Kuhn argues, by the advantages of the new theory. Once the new paradigm has been established, its principles are transmitted via the literature and scientific training. Normal science: Often suppresses fundamental novelties because they are necessarily subversive of its basic commitments. Nevertheless, so long as those commitments retain an element of the arbitrary, the very nature of normal research ensures that novelty shall not be suppressed for very Iong (5).

Although paradigm change is resisted, it is the existence of a paradigm which permits scientific progression; it allows for both the fuaher explorations of the concepts and relationships posited by existing theory, and the radical re-conception of these as anomalies become apparent. Although the paradigm is a precursor of change, alternative theories will not usually be formulated by the adherents to the conventional view, but by those outside it. Helen Longino (1990) departs from both the Kuhnian account of scientific practice, and the realist account, which holds that theories in the "mature" sciences, such as physics, are approximately true. In Science as Social Knowledge, Longino argues that scientific practice involves two types of values, constitutive and contextual. Constitutive values are the goals which science seeks to attain, such as truth, scope, accuracy, and fruitfulness. They are "the source of the rules determining what constitutes acceptable scientific practice or scientific method" (4). Since these goals are assumed to be the prerogative of science, they are often not regarded as "values." Contextual values, on the other hand, "belong to the social and cultural environment in which science is done"; they consist in "group or individual preferences about what ought to be" (4). Longino argues that there is a necessary connection between the background assumptions that we bring to the reading of scientific - and everyday - evidence and the conclusions we draw from it. Consequently, she states that "evidential reasoning is always context dependent, that data are evidence for a hypothesis only in the light of background assumptions that assert a co~ectionbetween the sorts of thing or event that the data are and the processes or states of affairs described by the hypothesis7'(215). Background assumptions do not always encode social values, but do provide a means by which these values may enter the reasoning process. Her approach differs from a Kuhnian one because this does not mean that the object of observation itself changes depending on the contextual framework through which it is viewed, but that different aspects of the object will become sibmcant depending upon our background assumptions. A piece of evidence may be used to support a number of hypotheses. Which hypothesis it is used to support therefore is not dependent merely on the evidence itself but the background hypothesis used to connect the two. Scientists approaching the same piece of evidence from two different perspectives do not "see" two different things, but different aspects of the same thing; what is significant about the object for one, is not necessarily significant for the other. Also, 'Tt is not always the case that the same body of evidence supports different theories - different features may constitute evidence for a different hypothesis" (54). Longino rejects Kuhn's incommensurability

thesis because:

If theories are really incommensurable, we cannot make the initial judgement that they offer incompatibIe explanations of the same phenomena, for we have no way to justify judgements of compatibility and incompatibility, difference or sameness. (28)

Although what counts as "evidencey7for a particular hypothesis will depend on background assumptions, these assumptions can still be differentiated from the evidence, and the hypothesis which it has been taken to support. Longino argues that objectivity is a social property. She distingguishes between objectivity as a characteristic of the scientific method, and objectivity as a characteristic of individual practitioners. To say that something is objective means that it "reflects the critically achieved consensus of the scientific community" (74). If socially-produced objectivity is to be achieved, it must be capable of transforming both individual and communal scientific practice, which entails the existence of recoopized fora for criticism, shared standards, and shared intellectual authority. The diversity of the community strengthens objectivity by increasing the number of perspectives brought to bear on scientific practice. Longino refers to her approach as "contextual empiricism," which is empiricist in treating experience as the basis of knowledge claims in the sciences...[ and] contextual in its insistence on the relevance of context - both the context of assumptions that supports reasoning and the social and cultural context that supports scientific inquiry - to the construction of knowledge. (2 19) I use Longino's concept of contextual empiricism to analyze the rbGH case. The interpretation of the rbGH data depended on two kinds of assumptions; those based on Kuhnian "normal" science, and those based on judgements about the context into which the product was to be introduced. I will use the tern contextual knowledge, rather than contextual values, in order to capture the nature of the latter kind of judgements. These judgements depended on howledge about practices within that context, as well as implicit values about their acceptability.

Longino's position can be distin,pished from that of analysts from the social constructivist school, such as Latour and Woolgar (1979) and Knorr-Cetina (198 1). These analysts suggest that science is as thoroughly imbued with value judgements, and as reflective of social relationships, as any other human activity. Latour and Woolgar have investigated "the socially available procedures for constructing an ordered account out of the apparent chaos of available perceptions" (33). They conclude that the acceptance of an account is not determined by its utility in explaining a particular state of affairs, but by social factors. The production of credible information occurs through a competitive rather than a communal process by which rival interpretations are eliminated. This process of elimination is dependent on the resources available to defeat alternative explanations. As one account becomes accepted, the economic costs of raising an objection to it increase, and the more difficult it becomes to raise the capital necessary to purchase the materials, equipment and labour time necessary in order to construct an alternative. Science is therefore not universal, but locally constructed. The local only becomes universal by virtue of the resources which enable the social process of elimination, and consequent acceptance, to proceed. Not ody, therefore, does science not deserve special status, but the granting of such status to science blinds us to the way in which scientific facts are constructed. Latour and Woolgar note that "it is because the controversy settles that a statement splits into an entity and a statement about an entity; such a split never precedes the resolution of controversy" (180). I argue, however, that it is possibLe to isolate something deserving of the name science (putting aside the question of science's status) in the decision-making over rbGH, and that the object of investigation and the controversy can be distinguished.

2.3. Political economy of agriculture literature Given that one of the world's largest agricultural biotechnology and seed companies, Monsanto, is the producer of rbGH, one might expect the science policy relations in this case to be shaped most importantly by the political economy of agriculture. In Chapter Two of the thesis, a brief outline of the political economy of agricultural biotechnology will be given to provide background information to the study, and because its influence is important. Political economy does not determine the outcome in this case; rather I use the political economy of agriculture Literature to understand this context. In the 1980s, most commentators agreed that agriculture was in a period of crisis characterized by reduced farm numbers, fahgincomes, and trade conflict. Analysts studying the political economy of agriculture have explained this crisis by tracing the historical deveiopment of the global food production system and its relation to broader economic structures. The central point is that prevailing industrial production practices also affect the food system. Kemey et al. (199 1) have argued that: Historically, the effective inteamtion of agriculture into the Fordist economy resulted in great part from political solutions to the overproduction crisis of the 1920s and 1930s, most specifically in response to the Great Depression. This crisis was partially solved by transforming farmers, traditionally self-reproductive producers, into consumers of mass-produced inputs ranging from petrochemical fertilizers to farm machinery (174). The U-S. supported agriculture through price support, marketing, and supply management programs. Price support and credit policies enabled farmers to purchase industrial inputs such as agricultural chemicals and machinery, as well as processed food. Agriculture thereby became connected into the Fordist system of production, in which mass production and mass consumption were linked. The farm crisis of the 1980s is to be understood as part of a wider breakdown in the Fordist production system, in which the mass production/mass consumption dyad and its complementary foxms of domestic regulation could no longer be sustained. Although these policies aimed to protect domestic agriculture, Harriet Friedmann (1991) has argued that their implementation facilitated the integration of food sectors across national lines. The formation of a giobaI food reghe - which Harriet Friedrnann defines as "a rule-governed structure of production and consumption of food on a world scale" - extended the U.S J Fordist model internationally (1993: 30). The food regime is a global system in which production and consumption may be nationally or internationally based. In a nationally-based food regime, production - at least in developed countries - is determined by agricultural policies which support local production and may involve protection measures and price supports. In a system organized along transnational lines, production is oriented toward a competitive global market. From 1947 to 1972, Friedmann argues, the food system was governed by a "surplus regime" based around the US. system of food production. The U.S. surplus system was comprised of three fwd complexes: the wheat complex, the "durable food" complex, and the Livestock complex. Each complex was characterized by different levels of state, and corporate, involvement in food production. In wheat, the U.S. protected its domestic markets and raised farm incomes through price supports. Government policy - and technological developments - created surpluses which were disposed of outside of markets, as food aid to the Third World, to avoid lowering prices. Under the "durable food" complex, corporations contracted with specialized farms for standard raw materials to be processed into packaged foods. The livestock complex was based around the increased production and consumption of meat, and the increased production of soy and maize as animal feed. Whereas European wheat production replicated US. national production, European livestock firms imported feed inputs from the U.S., creating an Atlantic ago-food sector around which the wodd food economy was reconfigured (1993: 37). Several factors led to the demise of the surplus regime. Massive Soviet grain purchases in the early 1970s created shortages which the U.S. responded to by encouraging debt-financed production. The breakdown of the 1970s was not automatically expressed in declining farm incomes. However, the breakdown of the regime led to the creation of massive debt in the farm sector and, later, even greater surplus problems. The breakdown of the Bretton Woods monetary system also destabilized the financial and monetary relations around which the regime was based. In the 1980s, the European Common Agricultural Policy (CAP) led to increased competition between European and subsidized US. grain markets (McMichael 1992: 349).

As the Fordist form of productiodregulation disintegrates, another form wiU, the literature suggests, come to replace it. Philip McMichael has contended that the new regime emerging from the breakdown of the post-war system is based around the internationalization of food production and distribution (McMichael 1992: 345). This global system, known as the ago-industrid production chain, divides food production into four processes: the use of inputs e.g. seeds, pesticides, machinery; agricultural production; industrial processing; and international distribution (Ruivenkamp 1988: 288). It consists in the increasing importance of transnational companies in food production, processing, and distribution; the integration of diverse localities through ago-food corporations' global sourcing strategies; and the changing of diets to reflect Western tastes. The internationalization of frnance and other sectors of capital has had implications for global reflatory mechanisms. McMichael argues that international regulatory systems such as the Uruguay Round of GATT negotiations and the increasing power of the IMF and the World Bank have facilitated capital accumulation on a global scale. States' compliance with the requirements of these regimes has created the "transnationalisation of the state"; meaning that state structures and policies are more responsive to the requirements of global capital than to the promotion and protection of domestic welfare. Under these circumstances, domestic agricultural policy has been directed away from the development of a coherent national sector, and towards integration into global production circuits

(McMichael 199 1: 83). This Literature aims to provide a unifying context for thinking about agriculture. Recent critiques, however, have argued that in the quest for a unifying theory, insufficient attention has been paid to the empirical reality of agricultural production. Goodman (1997) argues that globlization is not a single phenomena, but is comprised of several "world scale" processes-- "internationalization, multinationalization, transnationalization, and globalization - that operate concurrently, yet differently, in the world economy." (665) Goodman points out that the ideology of competitiveness is likely to lead, not to global economic inteagation, but to greater regional integration within the triad of North America, Western Europe, and South-East Asia. World-scale processes transform states and regions unevenly, suggesting that there is greater room for variation among institutional structures and productive forms than the globalization literature suggests. Similarly, Robert Wade (1996) argues that two important measures of economic integration, trade and foreign direct investment, show a high degree of concentration among developed countries; where North-South integration does take place, it is highly regionalized. Wade also argues that resources, such as skill, capital, and technology, are relatively immobile. For example, not only are multinationals tied more closely to their home base than much of the literature suggests, but they are not entirely mobile with respect to the territories they invest in. Evidence of the regionalization, and the unevenness of internationalization, is found in the rbGH case. Due to different political structures, the policy issue has been dealt with differently in Europe than in North America. With respect to dairy production, regional agreements and international agreements have conflicted; ironically, the primacy of the international agreement has protected the Canadian dairy industry Erom a US. challenge under the North American Free Trade Agreement (NAFTA). Although an ideology of global competitiveness has been extremely important to both government policy and corporate strategy in both the U.S. and Canada, this has played out differently in the two countries. The Canadian dairy industry is still protected from external competition, Canadian exports are minimal, and the supply management system is in place. In the US., on the other hand, the debate about rbGH was simultaneously a debate about the necessity for technological innovation in response to the increasing importance of market mechanisms. 3. Methodology In order to explore the social and political background to the decision-making process regarding rbGH, as well as the process itself, I examined both US. and Canadian government documents pertaining to both the facilitation, and regulation, of biotechnology, including relevant statutes and administrative ,~delines,and, in the U.S. case, Congressional hearings regarding particularly controversial decisions and trends, such as the patenting of animals and the commercialization of scientific research. In regard to the rbGH debate, I also researched the Congressional and Parliamentary hearings into the subject, and, for the US., the various advisory committee meetings regarding human health implications, labelling issues, and the post-approval monitoring [email protected] dso covered the various General Accounting Office and Department of Health and Human Services Inspector-General's reports, and, for Canada, the House of Commons Agriculture and A,giFood Committee reports, government response, and rbST Task Force reports. The political economy of biotechnology development was researched through documents from the Monsanto company, including annual reports and internal publications, newspaper articles, particularly from the Wall Street Journal and the chemical trade press, and the secondary literature. I also obtained reports, newsletters, and copies of correspondence from the various environmental, farm, and food policy groups opposed to the drug, including the Canadian

Institute for Environmental Law and Policy, the Toronto Food Policy Council, the Ram's Horn, Rural Vermont, and the U.S. National Farmers' Union. Information regarding the scientific debate was obtained primarily from the FDA's Freedom of Information Summary, and an earlier summary of the human health data and its interpretation, published in Science in August 1990. I also read articles from scientific journals including Science, The Lancet, Physiological Reviews, the Journal of Dairy Science, the Journal of the American Veterinary Medical Association. I also attended the final meeting of the FDA's Veterinary Medicine Advisory Committee (VMAC) which reviewed the data from the rbGH post-approval monitoring proem in November 1996. My conclusions are based primarily on data from interviews conducted between August 1996 and August 1997. I interviewed 26 individuals, several of whom were interviewed twice. Most of the interviews were conducted face-to-face; some were conducted over the phone due to geobgraphical or time constraints. I interviewed two scientists from the U.S. FDA, both of whom were prominent in the rbGH evaluation, and two other FDA officials. My informant regarding the Canadian regulatory process was the former chief of the division responsible for the animal health review. I spoke with four Monsanto scientists, and the company's Director of Regulatory Aff',who interacted with the FDA and spoke at Canadian Parliamentary hearings. I also spoke to scientists at universities in Canada and the U.S. who acted as principal investigators for the safety and efficacy trials, one university scientist who had been critical of the process, and members of professional associations (such as the American Medical Association) who authored position statements endorsing the product. In addition, I interviewed biomedical researchers outside the rbGH debate who were investigating growth factor physiology in order to contrast their methodology with that of scientists in the debate. I located these individuals by contacting the authors of scientific articles and the participants in Congressional and Parliamentary hearings; requesting names from the relevant institutions; and obtaining referrals from other interviewees. I had no Wiculty obtaining interviews with scientists outside the debate. Since the drug is still under review in Canada, and hence the confidentiality of the information submitted in support of the drug application must be maintained, I was unable to obtain interviews with current Health Canada scientists. I was also unable to obtain interviews with some of the drug's critics, and one of the university scientists whose perspective I particularly wanted to obtain. Some of the people I wished to contact could not be reached, and many of the interviews were difficult to obtain. The FDA and Monsanto were initially reluctant to participate. They received copies of the questions before participating, and the

FDA's counsel reviewed the questions beforehand. Lnterviewees were instructed that they could refuse to answer any question, and they often were unable to provide specific details in response to a particular query, but responded in generalities. Quotes attributed to particdar individuds were sent back to them for confiiation and correction; most of the

interviewees replied, with minor alterations.

A standard format provided the basis for the interviews. The questions focused on: whether a literature review was conducted and how it was decided what literature was relevant; how the scientists decided what kinds of studies should be conducted; how they

proceeded with the analysis of the data; what time period they worked within, and how this affected their analysis; what kinds of evidence would enable them to conclude that a

produ